1. Field Of The Invention
The present invention relates to devices for measuring oxygen mixed in fluids, and particularly to measuring the rate of oxygen permeation through blood plasma.
2. Prior Art
Conventional devices for detecting oxygen mixed with other gases or dissolved in a liquid have used an electrochemical cell with an oxygen permeable membrane adjacent the cathode. The sample of fluid to be analyzed is placed on the outside of the membrane. Oxygen diffuses through the membrane, into the electrolyte, and is reduced at the cathode, causing an electron flow to the anode. The cell may be either Galvanic, with a voltage increase towards the anode and generating electricity, or polarographic with a voltage decrease towards the anode and requiring an external power supply. Either way, the resultant current is proportional to the amount of oxygen diffusing through the membrane, and is thus a measure of the partial pressure of oxygen in the sample fluid. However, electrochemical probes are slow to reach an equilibrium value in contact with a specimen, particularly a blood specimen. During the interim, the consumption of oxygen in the electrolytic reaction lowers the concentration of oxygen in the sample and distorts the measurement.
Prior art blood-oxygen detectors have tried to avoid altering the sample oxygen partial pressure (pO.sub.2) by stirring as in U.S. Pat. No. 4,209,300, or by using a Clark-type polarographic cell with an extremely small cathode surface as in U.S. Pat. Nos. 4,209,300 and 4,207,146. Besides minimizing oxygen consumption, detectors disclosed in U.S. Pat. No. 4,042,465 (Morong), U.S. Pat. No. 4,120,770 (Kessler), U.S. Pat. No. 3,929,588 (Parker), and U.S. Pat. No. 4,264,328 (Marsoner) compensate for consumption in calculating the partial pressure. In the latter three patents, this compensation assumes a fixed diffusion rate of O.sub.2 through blood.
Because the prior art devices measure the concentration (solubility) of oxygen by minimizing oxygen consumption and assuming a negligible or fixed diffusion value, they are unsuitable for measuring diffusion, or permeability, which equals the product of diffusivity and solubility. In measuring diffusion or permeability, a tester must act as an oxygen sink and consume as much oxygen as possible, to create a concentration gradient. Oxygen consumption increases with current flow. Current through a Galvanic cell with a given load is limited by the intrinsic voltage potential of the cell. Polarographic cells are preferable for diffusion measurements because, with an appropriate external power supply, larger currents can be produced.
A diffusion cell is described by Thomas Robert Stein in Augmented Diffusion of Oxygen, Ph.D. Thesis, University of Minnesota, (1968) and also in Steady-State Oxygen Transport Through Red Blood Cell Suspensions, Journal of Applied Physiology, Vol. 31, No. 3, pp. 397-402 (1971). The Stein cell comprises a polarographic cell with a cathode formed from one end of a platinum cylinder 3/16 inch in diameter. The cathode is larger than in previous polarographic cells in order to permit a greater diffusion current and inherently more sensitive measurements. A silver anode disk, 1 1/16 inches in outside diameter with a 5/16 inch central hole, surrounds the cathode cylinder. The cathode and anode are held spaced by epoxy resin. The top surfaces of the cylinder, the epoxy, and the disk are in a common plane. The blood sample to be tested is held in a sample well with a TEFLON membrane over the cathode. Between the membrane and the cathode there is a layer of electrolyte-saturated filter paper. A chamber over the sample well allows the atmosphere over the sample to be controlled.
Using flat, annular, concentric and co-planar electrodes, the half-cell reduction reaction at the cathode in the prior art cell was expected to be: EQU O.sub.2 +2H.sub.2 O+4e.sup.- .fwdarw.4OH.sup.- ( 1)
and to take place as described by the "Nernst" equation: ##EQU1## where: E=observed half-cell e.m.f.
E.degree.=standard cell e.m.f. PA0 R=the gas constant PA0 T=the absolute temperature PA0 F=the faraday constant PA0 n=the number of electrons involved in the reaction, and PA0 Q=the reaction quotient.
However, due to various secondary effects, an unacceptably large and unpredictable current, hereinafter known as the residual current, flows through the electrolyte of the Stein cell even in the total absence of oxygen. Prior art detectors with low voltages and currents were able to compensate for residual currents by simply calibrating the detector current to zero in the absence of oxygen. However, in the larger cathode higher current Stein cell, the residual current is higher.
In addition, Stein appears to overlook the fact that the Nernst equation does not directly consider electrode surface charge distribution, in effect assuming that the distribution is consistently equal to the average. However, in a negatively charged electrode, electrons will repel each other and be concentrated in the points furthest from the centroid of the electrode. If the charge distribution is skewed sufficiently, then the increased concentration of electrons could cause an uncalculated reduction of other species in the electrolyte, such as hydrogen ions, and produce a residual current.
Another drawback of the Stein cell is that it will not hold a calibration when used with the commercially available Clark cell electrolyte, buffered KCl. The oxidation reaction at the anode is essentially: EQU 4Ag+4Cl.sup.- .rarw..fwdarw.4AgCl+4e.sup.-. (3)
This causes OH.sup.- to accumulate in the electrolyte, and deposits AgCl on the anode, and reduces the conductivity of the cell. These effects are tolerable in cells used with minimum current to measure oxygen concentration but with high currents the Stein cell will not stay in calibration.